Microstructural Characterization of Dry Powder Inhaler Formulations Using Orthogonal Analytical Techniques.

Purpose: For locally-acting dry powder inhalers (DPIs), developing novel analytical tools that are able to evaluate the state of aggregation may provide a better understanding of the impact of material properties and processing parameters on the in vivo performance. This study explored the utility of the Morphologically-Directed Raman Spectroscopy (MDRS) and dissolution as orthogonal techniques to assess microstructural equivalence of the aerosolized dose of DPIs collected with an aerosol collection device.

Methods: Commercial DPIs containing different strengths of Fluticasone Propionate (FP) and Salmeterol Xinafoate (SX) as monotherapy and combination products were sourced from different regions.

Simulation Informed Design and Performance of In Vitro Bioequivalence Trials for Particle Size Distributions.

This study used statistical simulations to investigate the performance of the population bioequivalence test applied to image-based particle size measurements (such as morphologically directed Raman spectroscopy) and methods for designing in vitro bioequivalence trials using prior information. Simulations of in vitro population bioequivalence trials were conducted across a range of representative D (number-weighted median particle diameter from a log-normal particle size distribution) and span (which is defined as [Formula: see text] where D and D are the number-weighted 90th and 10th percentiles in particle diameters sampled from a log-normal particle size distribution) values respectively. The performance of the population bioequivalence test in the simulations was driven by an interplay between overall test variability and the widening or narrowing of the bioequivalence region due to variance terms in the test statistic definition.

Stabilisation of water-in-water emulsions by montmorillonite platelets.

The formation of water-in-water emulsions from the aqueous two phase system containing polyethylene oxide and pullulan, stabilised by montmorillonite platelets, was investigated. A novel approach of preparing the emulsions at non-equilibrium polymer concentrations was successfully utilised to control viscosity during mixing and allow the use of low energy emulsification methods. Polyethylene oxide adsorbed to the platelets much more strongly than pullulan favouring the formation of pullulan-in-polyethylene oxide emulsions which remained stable for a period of weeks.

Controlling the Rheology of Montmorillonite Stabilized Oil-in-Water Emulsions.

The rheology of hexadecane-in-water emulsions stabilized by montmorillonite platelets was investigated. In these systems excess particles form a network in the continuous phase which strongly dictates their rheological behavior. The emulsions were modified by the addition of NaCl and NaPO to the continuous phase at varying concentrations.

Steady-state droplet size in montmorillonite stabilised emulsions.

The formation of hexadecane-in-water emulsions stabilised by montmorillonite platelets was studied. In this system the platelets form a monolayer around the droplets and the droplet size decreases with increasing platelet volume fraction. However, the number of platelets present exceeds that required for monolayer coverage.

Controlling Clusters of Colloidal Platelets: Effects of Edge and Face Surface Chemistries on the Behavior of Montmorillonite Suspensions.

The structural and rheological consequences of adsorbing pyrophosphate anions to the edges and polyetheramines to the faces of montmorillonite platelets in aqueous suspension were investigated. Oscillatory rheology and scattering experiments showed that the two surface treatments act in different regions of the phase diagram and that this can be attributed to modifications of local particle interactions resulting in changes to the behavior and morphology of platelet clusters. The polyetheramine was found to neutralize surface charge, reducing electrostatic repulsion between platelets and therefore allowing them to come into closer proximity.